Stem cells are a potentially important source of cells to replace tissues or organs deficient as a result of trauma, disease, or developmental anomalies. This proposal is focused on increasing our understanding of stem cells derived from adult bone marrow. The proposed experiments will examine the molecular mechanisms controlling nuclear reprogramming and plasticity of gene expression exhibited by adult bone marrow-derived cells. In Specific Aim (1) I plan to develop an in vitro system to model plasticity and nuclear reprogramming as they occur in vivo. Specific Aim (2) will involve an in depth investigation of the intracellular events that control or modulate the changes in gene expression resulting in different cellular phenotypes. Specific Aim (3) will use information gained from the above studies to identify the characteristics of hematopoietic stem cells and their derivatives that are responsible for their predilection to contribute to other tissues. The proposed experiments will not only enhance our basic knowledge of stem cell function, but may also result in new clinical approaches for treatment of conditions involving a deficit of tissue repair or regeneration.